The success of tamoxifen in prolonging survival and recurrence-free survival among breast cancer patients has initiated the study of its use in the primary prevention of breast cancer. However, the long-term risks associated with tamoxifen therapy have not been adequately evaluated, particularly with respect to subsequent cancer occurrence. Both beneficial and adverse health effects need to be well documented so that informed and responsible decisions can be made with respect to prophylactic therapy. This population-based, nested case-control study will examine whether tamoxifen use is a risk factor for cancer of the uterine corpus and/or ovary among women diagnosed with unilateral breast cancer. Additionally, the variation in the duration and/or recency of tamoxifen use will be examined as it relates to the subsequent occurrence of primary contralateral breast cancer. A cohort of women diagnosed with unilateral breast cancer between January 1, 1978 and December 31, 1990 will be identified from three urban counties included in the Cancer Surveillance System of western Washington, a population-based cancer registry. Women who subsequently developed a new primary malignancy of the contralateral breast n=235), ovary (n = corpus (n=45) as of December 31, 1991 will be selected as cases. A sample of women in this cohort who did not develop a second primary malignancy will be selected as controls. They will be matched to each case on the following characteristics of the case at initial breast cancer diagnosis: age, menopausal status, stage of cancer, and year of diagnosis. Tamoxifen therapy and other treatment information for the initial unilateral breast cancer, along with information on other potential risk factors for the subsequent new primary cancers of interest, such as parity, a family history of breast cancer, and prior exogenous hormone use, will be obtained by abstracting hospital medical records of cases and controls and through a self-administered questionnaire sent to physicians who were involved in each patients' care. Analyses will be conducted to compare the relative risk of each second primary cancer in relation to use of tamoxifen, adjusted for potentially confounding characteristics. A long follow-up period is necessary before randomized clinical trials can evaluate the risk of rare second cancers potentially associated with tamoxifen use. The proposed study can provide early results that will contribute valuable information to a broad spectrum of women as they consider the risks and benefits associated with prophylactic use of tamoxifen in the primary prevention of breast cancer.